The focus of this project is the treatment of depressed children with a tricyclic antidepressant. The subjects will be children aged 6-12 admitted to the Child Psychiatry Unit of the university hospital with a diagnosis of major affective disorder, depressed. Patients will be assessed during a brief baseline period by a structured diagnostic interview, by clinical evaluation by a child psychiatrist, and by rating scales for depression including Childhood Depression Inventory, Hamilton Rating Scale for Children, and clinical impression. Children evaluated as fulfilling DSM-III criteria for major-affective disorder and having depressive symptoms severe enough to warrant treatment will be enrolled in the study protocol. Children study protocol. Children will be treated in a random double-blind fashion with imipramine or placebo. Initially, imipramine subjects will be given 100 mg qhs as a starting dose. Their dose will then be adjusted by a laboratory psychiatrist after 2 weeks based on plasma blood levels obtained so that the plasma blood level will be within the proposed therapeutic range 125-225 ng/ml. Both placebo and imipramine subjects will be treated an additional four weeks, with the subjects and clinician remaining blind to treatment. Weekly assessment of the response to treatment and incidence and severity of adverse effects will be made and plasma samples will be obtained for continued drug analysis. At the end of the inpatient phase response rate of imipramine and placebo will be compared. Additionally, the response and adverse effects data will be plotted against drug concentration, including determination of both total and free drug, to determine: (a) whether there is an optimal concentration range for maximal response with minimal adverse effects, and (b) the effect of age on certain pharmacokinetic parameters. Phenomenological, familial, and demographic data will be collected at baseline to determine: (a) risk factors for the development of depression in children and (b) whether there are clinically useful prognosticators to distinguish patients responding to imipramine or placebo from those who do not. Finally, those children responding to imipramine or placebo will be followed both on and off drug to determine relapse rate and clinical course for one year.